We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Autologous LN-145 in Patients With Metastatic Non-Small-Cell Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04614103
Recruitment Status : Recruiting
First Posted : November 3, 2020
Last Update Posted : August 9, 2022
Sponsor:
Information provided by (Responsible Party):
Iovance Biotherapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE October 21, 2020
First Posted Date  ICMJE November 3, 2020
Last Update Posted Date August 9, 2022
Actual Study Start Date  ICMJE May 7, 2021
Estimated Primary Completion Date June 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 13, 2022)
Objective Response Rate [ Time Frame: Up to 60 months ]
To evaluate the efficacy of LN-145 as determined by objective response rate (ORR) in patients with metastatic NSCLC using the Response Evaluation Criteria in Solid Tumors (RECIST v1.1), as assessed by central review for Cohorts 1 and 2 and by the investigator for Cohort 3 and the Retreatment Cohort
Original Primary Outcome Measures  ICMJE
 (submitted: October 28, 2020)
Objective Response Rate [ Time Frame: Up to 60 months ]
To evaluate the efficacy of LN-145 in patients with metastatic NSCLC without an actionable driver mutation who have disease progression on or following a single line of approved systemic therapy consisting of combined immune checkpoint inhibitor(s) (CPI[s]) + chemotherapy ± bevacizumab, as determined by objective response rate (ORR), using the RECIST v1.1, as assessed by the Independent Review Committee (IRC) (Cohorts 1 and 2) or by the Investigator (Cohorts 3 and 4)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 13, 2022)
  • Objective Response Rate [ Time Frame: Up to 60 months ]
    To evaluate the efficacy of LN-145 as determined by objective response rate (ORR) per RECIST v1.1, as assessed by the Investigator for Cohorts 1 and 2
  • Complete Response Rate [ Time Frame: Up to 60 months ]
    To evaluate efficacy parameters such as Complete Response Rate (CRR) per RECIST v1.1
  • Duration of Response [ Time Frame: Up to 60 months ]
    To evaluate efficacy parameters such as Duration of Response (DOR) rate per RECIST v1.1
  • Disease Control Rate [ Time Frame: Up to 60 months ]
    To evaluate efficacy parameters such as Disease Control Rate (DCR) per RECIST v1.1
  • Progression-Free Survival [ Time Frame: Up to 60 months ]
    To evaluate efficacy parameters such as Progression-Free Survival (PFS) per RECIST v1.1
  • Overall Survival [ Time Frame: Up to 60 months ]
    To evaluate efficacy parameters such as Overall Survival (OS)
  • Adverse Events [ Time Frame: Up to 60 months ]
    To characterize the safety profile of LN-145 in patients with non-small-cell lung cancer (NSCLC)
  • Core Biopsies [ Time Frame: Up to 60 months ]
    To determine the feasibility of generating LN-145 using tumor tissue obtained via image-guided core biopsy
Original Secondary Outcome Measures  ICMJE
 (submitted: October 28, 2020)
  • Objective Response Rate [ Time Frame: Up to 60 months ]
    To evaluate efficacy parameters such as Objective Response Rate (ORR) per RECIST v1.1
  • Complete Response Rate [ Time Frame: Up to 60 months ]
    To evaluate efficacy parameters such as Complete Response Rate (CRR) per RECIST v1.1
  • Duration of Response [ Time Frame: Up to 60 months ]
    To evaluate efficacy parameters such as Duration of Response (DOR) rate per RECIST v1.1
  • Disease Control Rate [ Time Frame: Up to 60 months ]
    To evaluate efficacy parameters such as Disease Control Rate (DCR) per RECIST v1.1
  • Progression-Free Survival [ Time Frame: Up to 60 months ]
    To evaluate efficacy parameters such as Progression-Free Survival (PFS) per RECIST v1.1
  • Overall Survival [ Time Frame: Up to 60 months ]
    To evaluate efficacy parameters such as Overall Survival (OS)
  • Adverse Events [ Time Frame: Up to 60 months ]
    To characterize the safety profile of LN-145 in NSCLC patients, as measured by the incidence of Grade ≥ 3 treatment-emergent adverse events (TEAEs)
  • Core Biopsies [ Time Frame: Up to 60 months ]
    For Cohort 3 only: To evaluate the efficiency of generating LN-145 from tumor core biopsies; Percentage successful TIL products generated from core biopsies
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Autologous LN-145 in Patients With Metastatic Non-Small-Cell Lung Cancer
Official Title  ICMJE A Phase 2 Multicenter Study of Autologous Tumor Infiltrating Lymphocytes (TIL or LN-145) in Patients With Metastatic Non-Small-Cell Lung Cancer
Brief Summary This is a prospective, open-label, multi-cohort, non-randomized, multicenter phase 2 study evaluating LN-145 in patients with metastatic non-small-cell lung cancer
Detailed Description LN-145 is a ready-to-infuse TIL therapy that utilizes an autologous TIL manufacturing process, as originally developed by the NCI and further optimized by Iovance for the treatment of patients with metastatic NSCLC. The cell transfer therapy used in this study involves patients receiving a non-myeloablative (NMA) lymphodepleting preparative regimen, followed by infusion of autologous TIL, then finally followed by the administration of IL-2.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Non Small Cell Lung Cancer
Intervention  ICMJE
  • Biological: LN-145
    A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After lymphodepleting chemotherapy including cyclophosphamide and fludarabine, patient is infused with autologous TIL (LN-145), followed by IL-2.
    Other Name: TIL, Autologous Tumor Infiltrating Lymphocytes
  • Biological: LN-145
    A tumor sample is obtained by image-guided core biopsy from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After lymphodepleting chemotherapy including cyclophosphamide and fludarabine, patient is infused with autologous TIL (LN-145) followed by IL-2.
    Other Name: TIL, Autologous Tumor Infiltrating Lymphocytes
Study Arms  ICMJE
  • Experimental: Cohort 1
    Patients whose tumors did not express programmed cell death-ligand 1 (PD-L1), i.e., tumor proportion score (TPS) < 1% prior to ICI treatment and Patients with no available historical TPS for PD-L1 expression
    Intervention: Biological: LN-145
  • Experimental: Cohort 2
    Patients whose tumors expressed PD-L1 TPS ≥1% prior to ICI treatment
    Intervention: Biological: LN-145
  • Experimental: Cohort 3
    Patients, regardless of tumor PD-L1 TPS prior to ICI treatment, who are unable to safely undergo a surgical tumor resection for TIL generation
    Intervention: Biological: LN-145
  • Experimental: Retreatment Cohort
    Patients who were previously treated with LN-145 in Cohort 1, 2, or 3.
    Intervention: Biological: LN-145
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 28, 2020)
95
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2026
Estimated Primary Completion Date June 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Have historically or pathologically confirmed diagnosis of metastatic Stage IV NSCLC without EGFR, ALK, or ROS genomic alterations.
  • For patients who have actionable mutations (other than EGFR, ALK, or ROS genomic alterations), 1 additional line of therapy with the appropriate targeted therapy will be allowed.
  • Patients must have documented radiographic disease progression on or after the first-line therapy, including concurrent or sequential ICI and platinum-based chemotherapy ± bevacizumab. No more than 1 prior line is allowed if ICI and platinum-based chemotherapy were administered concurrently and no more than 2 prior lines are allowed for sequential administration of platinum-based chemotherapy and ICI as 2 separate lines.
  • LN-145 manufacture is allowed for patients who have residual resectable disease after completion of the platinum-based chemotherapy component of the front-line ICI and platinum-based chemotherapy combination and meet all eligibility criteria except documented disease progression. These patients must intend to receive TIL therapy after disease progression
  • Prior systemic therapy in the adjuvant or neoadjuvant setting, or as part of definitive chemoradiotherapy, will count as a line of therapy if the patient had disease progression during or within 12 months after the completion of such therapy.
  • At least 1 resectable lesion for TIL production and at least one remaining measurable lesion, as defined by RECIST v1.1
  • Have adequate organ function
  • LVEF > 45%, NYHA Class 1
  • Have adequate pulmonary function
  • ECOG performance status of 0 or 1
  • Patients of childbearing potential or those with partners of childbearing potential must be willing to practice an approved method of highly effective birth control during treatment and up to 12 months after all protocol-related therapy

Exclusion Criteria:

  • Patients who have EGFR, ALK or ROS driver mutations
  • Patients who have symptomatic, untreated brain metastases.
  • Patients who have had allogeneic organ transplant or prior cell therapy within the past 20 years
  • Patients who have any form of primary immunodeficiency
  • Patients who are on systemic steroid therapy ≥ 10 mg/day of prednisone or equivalent.
  • Patients who have received a live or attenuated vaccination within 28 days prior to the start of treatment
  • Patients who have had another primary malignancy within the previous 3 years
  • Participation in another interventional clinical study within 21 days
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Iovance Biotherapeutics Study Team 866-565-4410 Clinical.Inquiries@iovance.com
Listed Location Countries  ICMJE Canada,   Netherlands,   United States
Removed Location Countries Switzerland
 
Administrative Information
NCT Number  ICMJE NCT04614103
Other Study ID Numbers  ICMJE IOV-LUN-202
2020-003629-45 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Iovance Biotherapeutics, Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Iovance Biotherapeutics, Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Iovance Biotherapeutics Study Team Iovance Biotherapeutics
PRS Account Iovance Biotherapeutics, Inc.
Verification Date August 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP